DETERMINE (Determining Extended Therapeutic Indications for Existing Drugs in Rare Molecularly Defined Indications Using a National Evaluation Platform Trial) - Master Screening Protocol (DETERMINE)

THE PARTICIPANT MUST FULFIL THE ELIGIBILITY CRITERIA OUTLINED BELOW AND WITHIN THE SPECIFIC TREATMENT ARM APPENDIX TO WHICH THEY ARE ENROLLED. Core Inclusion Criteria Any patient with histologically proven locally advanced or metastatic cancer (solid tumour or haematological malignancy) who has: exhausted (or declined) standard-of-care treatment options. or for whom no effective standard treatment is available*. *In exceptional circumstances where upfront treatment on the CRUKD/21/004 DETERMINE trial is considered the best choice for the patient in the opinion of the Investigator, due to risk of considerable harm from standard treatment (e.g. where this involves mutilating surgery or is unacceptable due to patient age or genetic vulnerability such as CMMRD). and whose disease has progressed, or is refractory. Diagnosis of a rare cancer harbouring an actionable genomic alteration, or common cancer types with rare actionable genomic alterations, that have been identified using a validated sequencing technique and for which there is a relevant open treatment arm within the DETERMINE trial. Life expectancy of at least three months. Patients are able to provide written (signed and dated) informed consent and be capable of co-operating with treatment and follow-up. For patients under 16 years of age, the parent or legal guardian will be asked to provide written informed consent and the patient will be asked to provide age-appropriate assent (written or verbal, commensurate with age and level of understanding). Patients with objectively evaluable or measurable disease, according to an assessment method appropriate for their cancer type. Patients must provide a fresh tissue biopsy at baseline and blood samples for translational research. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (ECOG performance status 2 may be considered on an individual basis) (≥ 16 years), Karnofsky score ≥ 50% (12 years to 15 years) or Lansky Play scales ≥ 50% (<12 years). Please see specific treatment arm appendices for any variations on this criterion. Note: Patients <16 years: patients with Central Nervous System (CNS) tumours and a neurological deficit may be eligible with a performance status below 50%, at the discretion of the Investigator. In such cases, the deficit must be stable for at least 7 days prior to trial enrolment, be due to tumour or due to a post-surgical adverse event that is deemed by the local Investigator. Women of childbearing potential are eligible provided that they meet the following criteria: Have a negative serum or urine pregnancy test before enrolment and Agree to the birth control methods and duration of use of those methods, as specified in each treatment arm appendix. Male patients with partners of childbearing potential are eligible provided that they agree to the birth control methods and duration of use of those methods, as specified in each treatment arm appendix. Core exclusion criteria: Ongoing AEs >Common Terminology Criteria of Adverse Events (CTCAE) Grade 2 attributable to previous anti-cancer treatments. Exceptions to this are any ongoing toxic manifestation, which in the opinion of the Investigator should not exclude the patient. At high medical risk, in the opinion of the Investigator, because of non-malignant systemic disease (including active uncontrolled infection). Female patients who are pregnant, breastfeeding or planning to become pregnant or male patients with a partner who is a woman of childbearing potential and is planning to become pregnant during the trial or following the last dose of IMP, as specified in each treatment arm appendix. Is (or plans to be) a participant in another interventional clinical trial, whilst taking part in this trial. Participation in an observational trial which does not involve administration of an Investigational Medicinal Product (IMP) and which, in the opinion of the local Investigator, would not place an unacceptable burden on the patient would be acceptable e.g. sample collection* or Quality of Life (QoL) studies. *for paediatric patients participating in other studies involving tissue/circulating tumour (ct) DNA/other blood collection, consideration would need to be given to the total blood volumes collected (as per the European Medicines Agency blood volume limits for children). Co-administration of anti-cancer therapies other than those administered in this trial. Radiotherapy (except for palliative reasons) or chemotherapy, endocrine therapy, nitrosoureas, mitomycin-C, immunotherapy and molecularly targeted agents or other investigational medicinal products within 4 weeks or 5 half-lives (whichever is the shorter). Rapidly progressing or symptomatically deteriorating brain metastases. Patients with previously treated brain metastases are eligible, provided the patient has not experienced a seizure or had a clinically significant change in neurological status within the two weeks prior to registration. Such patients must be non-dependent on steroids or on a stable or reducing dose of steroid treatment for at least 14 days (or 7 days for paediatric patients) prior to trial enrolment. Primary brain or CNS malignancies are allowed providing the patient is clinically stable (if requiring corticosteroids must be at stable or decreasing doses for at least 14 days for adults and 7 days for paediatric patients prior to the start of IMP administration). Patients who have received brain irradiation must have completed whole-brain radiotherapy and/or stereotactic radiosurgery at least 14 days prior to the start of IMP administration. Any other condition which, in the opinion of the local Investigator, would not be in the best interests of the patient.